22-24495397-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016327.3(UPB1):​c.-7C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,612,786 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

UPB1
NM_016327.3 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.48
Variant links:
Genes affected
UPB1 (HGNC:16297): (beta-ureidopropionase 1) This gene encodes a protein that belongs to the CN hydrolase family. Beta-ureidopropionase catalyzes the last step in the pyrimidine degradation pathway. The pyrimidine bases uracil and thymine are degraded via the consecutive action of dihydropyrimidine dehydrogenase (DHPDH), dihydropyrimidinase (DHP) and beta-ureidopropionase (UP) to beta-alanine and beta-aminoisobutyric acid, respectively. UP deficiencies are associated with N-carbamyl-beta-amino aciduria and may lead to abnormalities in neurological activity. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 22-24495397-C-G is Benign according to our data. Variant chr22-24495397-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 340927.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UPB1NM_016327.3 linkuse as main transcriptc.-7C>G 5_prime_UTR_variant 1/10 ENST00000326010.10 NP_057411.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UPB1ENST00000326010.10 linkuse as main transcriptc.-7C>G 5_prime_UTR_variant 1/101 NM_016327.3 ENSP00000324343 P1
UPB1ENST00000382760.2 linkuse as main transcriptc.-7C>G 5_prime_UTR_variant 1/45 ENSP00000372208
UPB1ENST00000415388.5 linkuse as main transcriptc.-7C>G 5_prime_UTR_variant, NMD_transcript_variant 1/95 ENSP00000400684

Frequencies

GnomAD3 genomes
AF:
0.00152
AC:
231
AN:
152236
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000850
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00281
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00156
AC:
388
AN:
249428
Hom.:
2
AF XY:
0.00157
AC XY:
212
AN XY:
135064
show subpopulations
Gnomad AFR exome
AF:
0.000248
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00124
Gnomad FIN exome
AF:
0.000246
Gnomad NFE exome
AF:
0.00283
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00212
AC:
3092
AN:
1460432
Hom.:
5
Cov.:
33
AF XY:
0.00209
AC XY:
1516
AN XY:
726610
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000447
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00114
Gnomad4 FIN exome
AF:
0.000442
Gnomad4 NFE exome
AF:
0.00259
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
AF:
0.00152
AC:
231
AN:
152354
Hom.:
2
Cov.:
32
AF XY:
0.00134
AC XY:
100
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000849
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00281
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00141
Hom.:
0
Bravo
AF:
0.00139
EpiCase
AF:
0.00305
EpiControl
AF:
0.00279

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Deficiency of beta-ureidopropionase Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.54
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200677387; hg19: chr22-24891365; API